JP2019210246A - 神経伸長抑制剤 - Google Patents
神経伸長抑制剤 Download PDFInfo
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- JP2019210246A JP2019210246A JP2018107611A JP2018107611A JP2019210246A JP 2019210246 A JP2019210246 A JP 2019210246A JP 2018107611 A JP2018107611 A JP 2018107611A JP 2018107611 A JP2018107611 A JP 2018107611A JP 2019210246 A JP2019210246 A JP 2019210246A
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- Prior art keywords
- nerve elongation
- lpa
- nerve
- acid
- elongation inhibitor
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- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
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- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
[1.実験方法]
表皮細胞(ヒト正常表皮角化細胞、NHEKs)を1.5×104 cellsの播種密度で播種した。培地として倉敷紡績株式会社製HuMediaKG2培地を用いた。倉敷紡績株式会社製HuMediaKB2培地で希釈した日光ケミカルズ株式会社製「LPA」(LPA含量25質量%)を表1に示す最終濃度となるよう添加し、上記雰囲気下で24時間培養を行った。その後、TaqMan(登録商標) Gene Expression Cells−to−CTTM Kitのプロトコルに準拠しcDNAを作成し、TaqMan(登録商標) Gene Expression Assayを用いて、当該キットのプロトコルに準拠し、Sema3Aの発現量をReal time RT−PCR法(アプライドバイオシステムズ社製)にて測定した。なお、プライマーとしては、Assay ID: Hs00173810を使用した。表1中、Sema3Aの発現量を、LPA未添加コントロールの発現量を1とした相対比で表した。なお、統計処理はStudent−t検定を用いて解析を行った。表1中、Meanは平均値を、S.D.は標準偏差を、t−testはt検定におけるコントロールに対する有意差を、それぞれ示す。
表1に示すように、LPA未添加(コントロール)と比較して、LPAを添加した表皮細胞では、添加濃度依存的にSema3A発現量の顕著な増加が認められた。このことから、LPAによる神経伸長の抑制効果が期待された。
[1.実験方法]
大気汚染物質として、アメリカ国立標準技術研究所(NIST)より購入した標準参照物質SRM1975(Diesel Particulate Extract)を用いて評価を行った。SRM1975の詳細については、NISTのウェブサイトより入手可能である。
表2に示すように、SRM1975のみを添加して培養した表皮細胞の培養上清を用いた場合には、コントロールに比べて、神経細胞の突起の伸長が認められた。培養上清中のNGF量を評価したところ、コントロールは2.4±0.0(pg/μg protein)、SRM1975のみ添加は3.3±0.2(pg/μg protein)であったことから、SRM1975によってNGFの分泌が促進され、神経伸長が発現したものと示唆される。
(A)カルボマー2%水溶液 5.0(質量%)
キサンタンガム2%水溶液 5.0
ポリオキシエチレンメチルグルコシド(10EO) 5.0
LPA 0.1
クエン酸1%水溶液 3.0
クエン酸ナトリウム%水溶液 0.3
水 残量
(B)水 16.0
水酸化カリウム10%水溶液 0.34
(C)プロパンジオール 8.0
NIKKOLセラリピッドW−2 0.1
PEG−60水添ヒマシ油 0.5
防腐剤 適量
※NIKKOLセラリピッドW−2:PPG−4セテス−20、ジプロピレングリコール(日光ケミカルズ社製)
(調製方法)A、B、Cをそれぞれ溶解した後、全て混合し均一にする。
(A)NIKKOL ニコムルスWO 3.0(質量%)
NIKKOL シルブレンド91 8.0
NIKKOL VB6−IP 0.1
シクロペンタシロキサン 10.0
マカデミアンナッツ油 1.3
ホホバ種子油 1.2
(B)濃グリセリン 6.0
1.3−ブチレングリコール 5.0
PEG−32 0.2
PEG−220 0.3
防腐剤 適量
(C)エタノール 3.0
ヒアルロン酸ナトリウム1%水溶液 1.5
ヒドロキシプロリン 0.2
キレート剤 適量
水 残量
(D)LPA 0.1
水 5.0
※NIKKOL ニコムルスWO:シクロペンタシロキサン、PEG−10ジメチコン、ジステアルモニウムヘクトライト、トコフェロール(日光ケミカルズ社製)
NIKKOL シルブレンド91:シクロペンタシロキサン、ジメチコン、(ジメチコン/ビニルジメチコン)クロスポリマー(日光ケミカルズ社製)
NIKKOL VB6−IP:トリスヘキシルデカン酸ピリドキシン(日光ケミカルズ社製)
(調製方法)A、B、C、Dをそれぞれ均一に溶解した後、B、C、Dを混合する。Aをホモ撹拌しながら、B、C、Dの混合物を徐々に添加し、乳化する。
(A)グリセリン 20.0(質量%)
1,3−ブチレングリコール 5.0
LPA 0.1
ペムレンTR−1 0.3
ヒドロキシエチルセルロース 0.08
防腐剤 適量
キレート剤 適量
水 残量
(B)NIKKOL レシノールS−10 2.0
NIKKOL MGS−BV2 1.0
NIKKOL セラリピッドPI236 1.0
NIKKOL シュガースクワラン 3.0
ジメチコン(6cs) 10.0
ジメチコン(350cs) 0.5
(C)水酸化カリウム 0.1
水 0.9
(D)ヒアルロン酸ナトリウム1%水溶液 1.0
水 5.0
(E)エタノール 5.0
水 5.0
※NIKKOL レシノールS−10:水添レシチン(日光ケミカルズ社製)
NIKKOL MGS−BV2:ステアリン酸グリセリル(日光ケミカルズ社製)
NIKKOL セラリピッドPI236:セラミドNG、イソステアリン酸フィトステリル、ベヘニルアルコール、ペンタステアリン酸ポリグリセリル−10、ステアロイルラクチレートナトリウム(日光ケミカルズ社製)
NIKKOL シュガースクワラン:スクワラン(日光ケミカルズ社製)
ペムレンTR−1:(アクリレーツ/アクリル酸アルキル(C10−30))クロスポリマー(日本ルーブリゾール社製)
(調製方法)A、Bをそれぞれ80℃に加温し、均一になるまで撹拌混合する。80℃でAを撹拌しながら、Bを加え、ホモミキサーで乳化する。さらにCを添加し、45℃まで冷却したところでDを添加する。さらに35℃まで冷却したところで、Eを添加し、終了とする。
(A)NIKKOL ニコムルス41 2.5(質量%)
NIKKOL MGS−BV2 1.0
NIKKOL バチルアルコール100 0.3
セトステアリルアルコール 1.0
ジエチルアミノヒドロキシベンゾイル安息香酸ヘキシル 2.0
メトキシケイ皮酸エチルヘキシル 10.0
ジメチコン(10cs) 3.0
イソノナン酸イソノニル 2.0
シクロペンタシロキサン 7.0
(B)酸化チタン、水酸化アルミニウム 6.0
顔料 適量
(C)グリセリン 5.0
ジプロピレングリコール 5.0
PEG1500 1.0
プラスティックパウダーD400 1.0
ステアロイルメチルタウリンナトリウム 0.5
ケイ酸(アルミニウム/マグネシウム) 0.5
水 残量
キレート剤 適量
防腐剤 適量
(D)キサンタンガム2%水溶液 15.0
(E)LPA 0.1
水 5.0
※NIKKOL ニコムルス41:ベヘニルアルコール、ペンタステアリン酸ポリグリセリル−10、ステアロイルラクチレートナトリウム(日光ケミカルズ社製)
NIKKOL MGS−BV2:ステアリン酸グリセリル(日光ケミカルズ社製)
NIKKOL バチルアルコール100:バチルアルコール(日光ケミカルズ社製)
PEG1500:PEG−6、PEG−32(第一工業製薬社製)
プラスティックパウダーD400:(HDI/トリメチロールヘキシルラクトン)クロスポリマー、シリカ(東色ピグメント社製)
(調製方法)A、Cを80℃まで加温し、それぞれ均一溶解させる。Bは均一に分散させる。Eは室温で溶解させる。BをCに加え、撹拌しながら、Dを加え、80℃でホモミキサー撹拌をしながら、Aを徐々に加える。添加終了後、80℃でホモミキサー4500rpm、5分間乳化する。40℃まで撹拌冷却し、Eを加え、35℃で終了とする。
Claims (3)
- リゾホスファチジン酸およびその塩の少なくとも1種を有効成分として含有する、神経伸長抑制剤。
- 前記有効成分を添加していないコントロールと比較してSema3A発現量が増加する、請求項1に記載の神経伸長抑制剤。
- 大気汚染物質による神経伸長を抑制する、請求項1又は2に記載の神経伸長抑制剤。
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Citations (2)
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JPH11100320A (ja) * | 1997-09-29 | 1999-04-13 | Risuburan:Kk | 皮膚外用剤 |
JP2011140442A (ja) * | 2010-01-05 | 2011-07-21 | Nikko Chemical Co Ltd | スルフヒドリルオキシダーゼ活性促進剤 |
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2018
- 2018-06-05 JP JP2018107611A patent/JP2019210246A/ja active Pending
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JPH11100320A (ja) * | 1997-09-29 | 1999-04-13 | Risuburan:Kk | 皮膚外用剤 |
JP2011140442A (ja) * | 2010-01-05 | 2011-07-21 | Nikko Chemical Co Ltd | スルフヒドリルオキシダーゼ活性促進剤 |
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J BIOL CHEM, vol. 274(52), JPN6021042371, 1999, pages 37046 - 37052, ISSN: 0004759632 * |
J BIOL CHEM, vol. 275(31), JPN6021042375, 2000, pages 23973 - 23980, ISSN: 0004759635 * |
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